ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5430T>G (p.Asp1810Glu)

gnomAD frequency: 0.00001  dbSNP: rs149828124
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000168091 SCV000218747 uncertain significance Familial adenomatous polyposis 1 2024-12-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1810 of the APC protein (p.Asp1810Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28944238). ClinVar contains an entry for this variant (Variation ID: 188182). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000766666 SCV000293248 uncertain significance not provided 2025-01-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Identified in a patient with colorectal cancer in published literature (PMID: 28944238); This variant is associated with the following publications: (PMID: 18199528, 28944238)
Ambry Genetics RCV000571060 SCV000667409 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-13 criteria provided, single submitter clinical testing The p.D1810E variant (also known as c.5430T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 5430. The aspartic acid at codon 1810 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration was identified in a cohort of individuals with colorectal cancer undergoing multi-gene panel testing (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl RCV000168091 SCV000785047 uncertain significance Familial adenomatous polyposis 1 2017-03-21 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000168091 SCV004019166 uncertain significance Familial adenomatous polyposis 1 2023-02-15 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000766666 SCV004219567 uncertain significance not provided 2023-05-07 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000004 (1/249670 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in affected individuals with colorectal cancer (PMID: 28944238 (2017)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.
All of Us Research Program, National Institutes of Health RCV003995606 SCV004834166 uncertain significance Classic or attenuated familial adenomatous polyposis 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 1810 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with colorectal cancer (PMID: 28944238). This variant has been identified in 1/249670 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mayo Clinic Laboratories, Mayo Clinic RCV000235919 SCV000691757 likely benign not specified no assertion criteria provided clinical testing

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